Canagliflozin impairs T cell effector function via metabolic suppression in autoimmunity.
Cell Metab
; 35(7): 1132-1146.e9, 2023 07 11.
Article
en En
| MEDLINE
| ID: mdl-37230079
ABSTRACT
Augmented T cell function leading to host damage in autoimmunity is supported by metabolic dysregulation, making targeting immunometabolism an attractive therapeutic avenue. Canagliflozin, a type 2 diabetes drug, is a sodium glucose co-transporter 2 (SGLT2) inhibitor with known off-target effects on glutamate dehydrogenase and complex I. However, the effects of SGLT2 inhibitors on human T cell function have not been extensively explored. Here, we show that canagliflozin-treated T cells are compromised in their ability to activate, proliferate, and initiate effector functions. Canagliflozin inhibits T cell receptor signaling, impacting on ERK and mTORC1 activity, concomitantly associated with reduced c-Myc. Compromised c-Myc levels were encapsulated by a failure to engage translational machinery resulting in impaired metabolic protein and solute carrier production among others. Importantly, canagliflozin-treated T cells derived from patients with autoimmune disorders impaired their effector function. Taken together, our work highlights a potential therapeutic avenue for repurposing canagliflozin as an intervention for T cell-mediated autoimmunity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Autoinmunes
/
Diabetes Mellitus Tipo 2
/
Inhibidores del Cotransportador de Sodio-Glucosa 2
Límite:
Humans
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2023
Tipo del documento:
Article
País de afiliación:
Reino Unido